Geriatric depression has a chronic or relapsing and remitting course leading to severe personal suffering, family disruption and public cost. Continuation of our longitudinal study will permit us to focus beyond the immediate affective symptomatology to the catastrophic consequences of the disorder, such as recurrent depressive symptomatology, cognitive impairment, disability and mortality as they occur in an old-old population. A total of 250 well characterized subjects (150 elderly depressives, 50 younger depressives and 50 elderly non-depressed controls) will be systematically followed for 4--10 years as they approach the end of their lives. The hypotheses of the proposed study are based on conclusive or preliminary findings of the ongoing project and are directed to specific outcomes, i.e., recovery of depression, residual depression, relapse/recurrence, low level depressive symptoms, cognitive deterioration, disability, well-being and mortality. The study was inspired by the classic British longitudinal investigations and was conceived during a period of mentorship with the late Gerald L. Klerman, M.D. With these influences, our design has integrated methodological advances of the NlMH Collaborative Depression Study with concerns specific to geriatric populations. We have made no changes in our original design except for the addition of rating instruments. After an extensive initial evaluation, the suspects have in-person assessments every 6 months and are contacted by telephone 3 months after each assessment. Depressive symptomatology, family history, medical health, cognitive impairment, disability, well being, social support, life events, personality and brain MRl are assessed. Antidepressant treatment is not controlled but is classified according to its intensity. While cognizant of the inherent confounds of a naturalistic treatment study, we believe that this approach is the appropriate methodology for an outcome study of very long duration. We bring to this project an effective and committed team experienced in follow-up investigation and advanced data analysis, the support and structure of a developing CRC targeted to studies of outcomes of geriatric affective disorders, and a large sample (N = 180 by the end of 5th year) followed for up to 4 years with a rigorous design and remarkably low attrition (1.75% per year). Our findings will be used to determine the prognosis of geriatric depression and improve the efficacy of treatment and prevention by identifying high-risk groups and by introducing therapeutic interventions during periods of vulnerability. Moreover, elucidating relationships among depression, poor medical health, cognitive deterioration and disability can lead to models of treatment and prevention that integrate medical and psychiatric therapies with rehabilitation approaches.